RESUMO
Introduction: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease. As a clinical empirical prescription of traditional Chinese medicine, Qushi Huayu decoction (QHD) has attracted considerable attention for its advantages in multi-target treatment of NAFLD. However, the intervention mechanism of QHD on abnormal lipid levels and gut microbiota in NAFLD has not been reported. Methods: Therefore, we verified the therapeutic effect of QHD on high-fat diet (HFD)-induced NAFLD in rats by physiological parameters and histopathological examination. In addition, studies on gut microbiota and serum lipidomics based on 16S rRNA sequencing and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) were conducted to elucidate the therapeutic mechanism of NAFLD in QHD. Results: The changes in gut microbiota in NAFLD rats are mainly reflected in their diversity and composition, while QHD treated rats restored these changes. The genera Blautia, Lactobacillus, Allobaculum, Lachnoclostridium and Bacteroides were predominant in the NAFLD group, whereas, Turicibacter, Blautia, Sporosarcina, Romboutsia, Clostridium_sensu_stricto_1, Allobaculum, and Psychrobacter were predominant in the NAFLD+QHD group. Lipid subclasses, including diacylglycerol (DG), triglycerides (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylserine (PS), lysophosphatidylinositol (LPI), and phosphatidylglycerol (PG), were significantly different between the NAFLD and the control groups, while QHD treatment significantly altered the levels of DG, TG, PA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and platelet activating factor (PAF). Finally, Spearman's correlation analysis showed that NAFLD related differential lipid molecules were mainly associated with the genera of Bacteroides, Blautia, Lachnoclostridium, Clostridium_sensu_stricto_1, and Turicibacter, which were also significantly correlated with the biological parameters of NAFLD. Discussion: Taken together, QHD may exert beneficial effects by regulating the gut microbiota and thus intervening in serum lipids.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , RNA Ribossômico 16S/genética , Cromatografia Líquida , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , TriglicerídeosRESUMO
PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.